Experimental models of thymic leukemia are being used to define genetic, virologic and immunologic factors in leukemogenesis. In the leukemia-prone AKR thymus, ecotropic and xenotropic viruses are expressed which generate recombinant leukemogenic viruses. Expression of the two "precursor viruses" is severely restricted in the thymuses of leukemia resistant (AKRxNZB)F1 hybrid mice due to an NZB-derived genetic influence. Thymic graft and bone marrow chimeras were done to establish that this influence is exerted by thymic epithelial cells. The AKR thymic epithelium can induce the expression of retroviral genes and changes in thymocyte differentiation, whereas the (AKRxNZB)F1 thymic epithelium is deficient in this regard. The nature of the thymic epithelial inductive signal is being studied.